Traditionally, glass reaction vessels packed with a glass filter therein have been used in automated stepwise synthesizers for peptide synthesis and other syntheses.
Various apparatuses are now commercially available for peptide synthesis by ordinary solid-phase methods. However, none of them is a peptide synthesizer; they are all apparatuses for production of protected peptide resin, resin being bound with an elongating side-chain-protected amino acid via peptide bond. Usually, synthesis proceeds automatically in the apparatus until this stage; however, cleavage, including deprotection, is essential to finally remove the desired peptide, which process is now carried out manually. Specifically, the produced protected peptide resin is removed from the reactor and then usually subjected to cleavage in a glass reaction vessel packed with a glass filter therein.
However, in such reaction vessels, which comprise a glass container and a glass filter placed therein, a problem arises because of the necessity for a pretreatment such as chromic acid mixture treatment or heat treatment at about 600.degree. C. before peptide synthesis has been achieved because the peptides are prone to adsorption on the glass wall or cause filter clogging. Moreover, such conventional glass reaction vessels are expensive so that they are not economically advantageous.
Also, in glass reaction vessels, another problem of troublesome operation has been noted out, e.g., a silicon coating treatment is needed before reaction particularly when a solid-phase resin is used, because the resin adheres on the upper wall due to static electricity etc. so that the reaction cannot be uniformly carried out, which results in incomplete synthesis.
In the case of small-scale synthesis involving a small amount of resin, i.e., synthesized peptide resin, resin transfer from the reaction vessel to another cleavage vessel at the time of cleavage causes mechanical loss, which leads to reduction in yield. If the reaction vessel is washed for the purpose of co-washing after cleavage to prevent such loss, additional procedures such as concentration are required after the cleavage reaction. On the other hand, even when a scavenger is used, if the mixture resulting from the cleavage reaction is concentrated, attack by an alkyl cation derived from the amino acid side chain protecting group takes place upon acidolysis, which in turn increases by-products, considerably lowers the yield of the desired product and even makes purification impossible.
Although it is a common practice to use a scavenger for the purpose of capturing the cation resulting from cleavage, the cleavage is often conducted again after determining the optimum conditions.
Also, it is a well-known fact that even though the protected peptide resin has been produced efficiently, a side reaction may take place during cleavage, which hampers the obtainment of the desired product or considerably lowers the yield; experience, including trial and error, is very important in this cleavage.
Accordingly, in the relevant industry, there has been demand for the development of a reaction vessel free of such problems for use in solid-phase synthesizers; however, there is currently no satisfactory one.